Microdialysis sampling coupled to on-line microbore liquid chromatography for pharmacokinetic studies

Microdialysis sampling has been coupled on-line to microbore liquid chromatography for pharmacokinetic investigations in awake, freely-moving animals. Valve systems are described which provide continuous collection of the microdialysis sample for injection into the chromatographic system. One valve system consisted of two six-port valves used in tandem. The other valve system consisted of an eight-port valve with two sample loops. The eight-port valve system provided better precision than the dual six-port valve system yet worse than an autosampler. However, when used for dialysis samples, the precision of the various injection methods was equivalent. The on-line system was capable of rapidly following changes in the dialysate concentration and provided near real-time analysis of the plasma concentration of analytes. The system was evaluated by monitoring the pharmacokinetics of acetaminophen in awake, freely-moving rats.